My goal is to become a successful independent investigator pursuing my interests in mechanisms by which cells deal with environmental agents Currently, as a newly appointed Associate Professor, my efforts are divided between teaching, administrative responsibilities and research. The University of South Alabama is a small medical school with a limited faculty, however the student contact hours and the number of committees required to operate the medical school are the same as bigger universities with larger faculties. Therefore, I am compelled to participate in a greater proportion of teaching and administrative activities than developing faculty at many other medical schools. My major instructional responsibility is in Medical Gross Anatomy (over 180 student contact hours per year). Additionally, I am the course director and teach in a summer minority program and am involved in the teaching and training of graduate students. Consequently, I have the heaviest teaching load of any Associate Professor in the College of Medicine conducting funded research. l also have a significant service commitment. l currently serve on 13 university or departmental committees. In spite of these extensive commitments, my research career has progressed logically. Funding has been from first a NIH Postdoctoral Fellowship, then a Junior Faculty Research Award from the American Cancer Society, from which I was able to obtain a ROl from NIH that has just been renewed and serves as the basis for the research plan in this proposal. An Independent Scientist Award would free me from a large portion of these teaching and administrative commitments so that I could concentrate on the development of my full research potential at this critical stage in my career. Because of the dearth of information concerning DNA repair in the central nervous system this area is currently my primary research focus. Normal functioning in CNS cells, as in all cells, is dependent upon genomic stability. Yet, cellular genomes are constantly exposed to external agents such as environmental chemicals that modify DNA. Investigating the types of lesions formed and their repair are of prime importance in determining the impact that exposure to specific toxins will have on particular target cells. Therefore, the objective of the research in this proposal is to explore the factors which regulate damage and repair of specific lesions in DNA o CNS cells. Three specific aims are proposed. The first is to investigate repair of alkylation damage The second aim is to evaluate the formation and repair of reactive oxygen radical- induced DNA damage. The third aim will examine the formation and repair of nitric oxide-induced DNA damage. These studies will assess repair of certain DNA adducts across the entire genome within specific DNA sequences, and at the level of individual nucleotides in unique populations of glial cells. When successfully completed these studies will enhance our understanding of the role that environmental toxins play in the etiology and pathogenesis 1 of diseases of the CNS.